Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3 –E334K

AbstractThe mutationMYBPC3–E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity ofMYBPC3–E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype–genotype correlations in subjects with or withoutMYBPC3–E334K alone. The prevalence ofMYBPC3–E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutationMYBPC3–E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboringMYBPC3–E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutationMYBPC3–E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women,p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10,p = 0.062). The variantMYBPC3–E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring s...
Source: Heart and Vessels - Category: Cardiology Source Type: research